1 Department of Integrative Biology, University of California Berkeley, Berkeley, California, United States of America, 2Department of Biology, University of Copenhagen, Copenhagen, Denmark, 3 BGI-Shenzhen, Shenzhen, China, 4 Department of Statistics, University of California Berkeley, Berkeley, California, United States of America, 5 Beijing Institute of Genomics, Chinese Academy of Science, Beijing, China, 6 The Graduate University of Chinese Academy of Sciences, Beijing, China, 7 University of Pennsylvania, Philadelphia, Pennsylvania, United States of America, 8 The Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark, 9 Hagedorn Research Institute, Gentofte, Denmark, 10 Research Centre for Prevention and Health, Glostrup University Hospital, Glostrup, Denmark, 11 Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark, 12 Steno Diabetes Center, Gentofte, Denmark, 13 Department of General Practice, University of Aarhus, Aarhus, Denmark, 14 Department of Mathematics, University of Vienna, Vienna, Austria, 15 Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark, 16 Institute of Biomedical Science, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark, 17 Faculty of Health Sciences, University of Aarhus, Aarhus, Denmark

Abstract

A major question in evolutionary biology is how natural selection has shaped patterns of genetic variation across the human genome.Previous work has documented a reduction in genetic diversity in regions of the genome with low recombination rates.However, it is unclear whether other summaries of genetic variation, like allele frequencies, are also correlated with recombination rate and whether these correlations can be explained solely by negative selection against deleterious mutations or whether positive selection acting on favorable alleles is also required. Here we attempt to address these questions by analyzing three different genome-wide resequencing datasets from European individuals. We document several significant correlations between different genomic features. In particular, we find that average minor allele frequency and diversity are reduced in regions of low recombination and that human diversity, human-chimp divergence, and average minor allele frequency are reduced near genes.Population genetic simulations show that either positive natural selection acting on favorable mutations or negative natural selection acting against deleterious mutations can explain these correlations.However, models with strong positive selection on nonsynonymous mutations and little negative selection predict a stronger negative correlation between neutral diversity and nonsynonymous divergence than observed in the actual data, supporting the importance of negative, rather than positive, selection throughout the genome.Further, we show that the widespread presence of weakly deleterious alleles, rather than a small number of strongly positively selected mutations, is responsible for the correlation between neutral genetic diversity and recombination rate.This work suggests that natural selection has affected multiple aspects of linked neutral variation throughout the human genome and that positive selection is not required to explain these observations.

Author Summary

While researchers have identified candidate genes that have evolved under positive Darwinian natural selection,less is known about how much of the human genome has been affected by natural selection or whether positive selection has had a greater role at shaping patterns of variation across the human genome than negative selection acting against deleterious mutations. To address these questions, we have combined patterns of genetic variation in three genome-wide resequencing datasets with population genetic models of natural selection. We find that genetic diversity and average minor allele frequency are reduced in regions of the genome with low recombination rate. Additionally, genetic diversity, human-chimp divergence, and average minor allele frequency have been reduced near genes. Overall, while we cannot exclude positive selection at a fraction of mutations, models that include many weakly deleterious mutations throughout the human genome better explain multiple aspects of the genome-wide resequencing data. This work points to negative selection as an important force for shaping patterns of variation and suggests that there are many weakly deleterious mutations at both coding and noncoding sites throughout the human genome. Understanding such mutations will be important for learning about human evolution and the genetic basis of common disease.

Funding: The study was funded by Lundbeck Foundation and produced by The Lundbeck Foundation Centre of Applied Medical Genomics for Personalized Disease Prediction, Prevention, and Care (www.LuCAMP.org). The Novo Nordisk Foundation Center for Basic Metabolic Research is an independent Research Center at the University of Copenhagen partially funded by an unrestricted donation from the Novo Nordisk Foundation (www.metabol.ku.dk). KEL was supported by a Ruth Kirschstein National Research Service Award from the National Human Genome Research Institute (F32HG005308) and a Miller Research Fellowship from the Miller Research Institute at UC Berkeley. E Huerta-Sanchez was supported by a National Science Foundation Minority Postdoctoral Research Fellowship (DBI-0906065). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing interests: The authors have declared that no competing interests exist.

Darwin’s Other Bulldog: Charles Kingsley and the Popularisation of Evolution in Victorian England

Rev. Charles Kingsley 1819-1875

Piers J. Hale

Abstract

The nineteenth-century Anglican Priest Charles Kingsley (1819–1875) was a significant populariser of Darwin’s theory of evolution by natural selection. Kingsley was successful in this regard because he developed such diverse connections throughout his career. In the 1840s he associated with Chartists and radical journalists; in the 1850s and 1860s he moved freely in scientific circles and was elected Fellow of the Linnean Society of London in 1856 and Fellow of the Geological Society of London in 1863. In 1859 he was appointed Chaplain in Ordinary to the Queen. In 1860 the Prince Consort was willing and able to secure Kingsley appointment as the Regius Professor of Modern History at Cambridge University and he subsequently became tutor to the Prince of Wales. Thereafter he was frequently invited into high Victorian Society. A friend of ‘Darwin’s Bulldog’ Thomas Huxley, of the eminent geologist Charles Lyell and a correspondent of Darwin, at every turn he sought to promote Darwin’s ideas as theologically orthodox, a life-long campaign in which he was eminently successful.

"A celebrated author and divine has written to me that 'he has gradually learnt to see that it is just as noble a conception of the Deity to believe that He created a few original forms capable of self-development into other and needful forms, as to believe that He required a fresh act of creation to supply the voids caused by the action of His laws'." [Um autor e teólogo celebrado escreveu para mim que 'ele gradualmente aprendeu a ver que é nobre a concepção da Divindade acreditar que Ele criou algumas formas originais capazes de auto-desenvolvimento em outras formas necessárias, como crer que Ele precisou de um ato recente de criação para suprir as lacunas provocadas pela ação de Suas leis]

It has been hypothesized that neurological adaptations associated with evolutionary selection for throwing may have served as a precursor for the emergence of language and speech in early hominins. Although there are reports of individual differences in aimed throwing in wild and captive apes, to date there has not been a single study that has examined the potential neuroanatomical correlates of this very unique tool-use behaviour in non-human primates. In this study, we examined whether differences in the ratio of white (WM) to grey matter (GM) were evident in the homologue to Broca's area as well as the motor-hand area of the precentral gyrus (termed the KNOB) in chimpanzees that reliably throw compared with those that do not. We found that the proportion of WM in Broca's homologue and the KNOB was significantly higher in subjects that reliably throw compared with those that do not. We further found that asymmetries in WM within both brain regions were larger in the hemisphere contralateral to the chimpanzee's preferred throwing hand. We also found that chimpanzees that reliably throw show significantly better communication abilities than chimpanzees that do not. These results suggest that chimpanzees that have learned to throw have developed greater cortical connectivity between primary motor cortex and the Broca's area homologue. It is suggested that during hominin evolution, after the split between the lines leading to chimpanzees and humans, there was intense selection on increased motor skills associated with throwing and that this potentially formed the foundation for left hemisphere specialization associated with language and speech found in modern humans.

Received 15 November 2005; Accepted 6 December 2005. Available online 25 January 2006.

Abstract

The improbability of a spontaneously generated self-assembling molecule has suggested that life began with a set of simpler, collectively replicating elements, such as an enclosed autocatalytic set of polymers (or protocell). Since replication occurs without a self-assembly code, acquired characteristics are inherited. Moreover, there is no strict distinction between alive and dead; one can only infer that a protocell was alive if it replicates. These features of early life render natural selection inapplicable to the description of its change-of-state because they defy its underlying assumptions.Moreover, natural selection describes only randomly generated novelty; it cannot describe the emergence of form at the interface between organism and environment. Self-organization is also inadequate because it is restricted to interactions amongst parts; it too cannot account for context-driven change. A modified version of selection theory or self-organization would not work because the description of change-of-state through interaction with an incompletely specified context has a completely different mathematical structure, i.e. entails a non-Kolmogorovian probability model. It is proposed that the evolution of early life is appropriately described as lineage transformation throughcontext-driven actualization of potential (CAP), with self-organized change-of-state being a special case of no contextual influence, and competitive exclusion of less fit individuals through a selection-like process possibly (but not necessarily) playing a secondary role.It is argued that natural selection played an important role in evolution only after genetically mediated replication was established.

Although the point has already been emphasized by various authors that the assumption of descent with modification is not required to justify cladistics, recent debate suggests that there is still confusion surrounding the necessary and sufficient background knowledge underlying the method. Three general axioms necessary to justify cladistics—the discoverability of characters, hierarchy, and parsimony—are reviewed. Although the assumption of evolution is sufficient to justify cladistics, it is also sufficient to justify competing approaches like maximum likelihood, which suggests that the philosophical support for the cladistic approach is strengthened by purging reference to descent with modification altogether.

Communicated by Leslie Orgel, The Salk Institute for Biological Studies, San Diego, CA (received for review November 19, 1998)

Next Section

Abstract

A number of theories propose that RNA, or an RNA-like substance, played a role in the origin of life. Usually, such hypotheses presume that the Watson–Crick bases were readily available on prebiotic Earth, for spontaneous incorporation into a replicator.Cytosine, however, has not been reported in analyses of meteorites nor is it among the products of electric spark discharge experiments. The reported prebiotic syntheses of cytosine involve the reaction of cyanoacetylene (or its hydrolysis product, cyanoacetaldehyde), with cyanate, cyanogen, or urea. These substances undergo side reactions with common nucleophiles that appear to proceed more rapidly than cytosine formation. To favor cytosine formation, reactant concentrations are required that are implausible in a natural setting. Furthermore, cytosine is consumed by deamination (the half-life for deamination at 25°C is ≈340 yr) and other reactions. No reactions have been described thus far that would produce cytosine, even in a specialized local setting, at a rate sufficient to compensate for its decomposition. On the basis of this evidence, it appears quite unlikely that cytosine played a role in the origin of life. Theories that involve replicators that function without the Watson–Crick pairs, or no replicator at all, remain as viable alternatives.

Among the most commonly encountered ideas concerning the origin of life is the one that it involved an “RNA world” at an early stage (1). The term was coined by Gilbert (2), who also stated “The first stage of evolution proceeeds, then, by RNA molecules performing the catalytic activities necessary to assemble themselves out of a nucleotide soup.” The existence of such a soup has generally been taken for granted. For example, Eigen and Schuster (3) wrote “The building blocks of polynucleotides—the four bases, ribose and phosphate were available too under prebiotic conditions. Material was available from steadily refilling pools for the formation of polymers, among them polypeptides and polynucleotides.” The experimental evidence to date, however, does not appear to support such claims.

Many problems have arisen with both the prebiotic synthesis and the stability of ribose (4–9). To avoid the need for ribose, some authors have preferred to invoke an RNA-like polymer, with a simpler or more accessible backbone, at the start of life (6,10–16). A pre-RNA world would have come first, during which some substance of this type carried out the genetic functions later taken over by RNA. In the great majority of these theories, Watson–Crick pairing of A with U and of G with C is retained as the basis of genetic template recognition.

These suggestions still presume that the bases adenine, cytosine, guanine, and uracil were readily available on early Earth. I have argued that this presumption is not supported by the existing knowledge of the basic chemistry of these substances (4, 17). If the availability of the Watson–Crick pairs at the start of life appears implausible, then more attention must be given to theories that employ a very different replicator or no replicator at all.

To provide a firm basis for this conclusion, I have undertaken a series of reviews in which I consider in detail the chemical evidence for the availability of the Watson–Crick bases at the start of life. In a previous paper, however, I concluded that current information concerning the availability and chemical properties of adenine did not support the idea that it was used in a replicator at the start of life (17). In this publication, I wish to consider the prebiotic syntheses and the stability of cytosine.

Absence of Cytosine in Meteorites and Electrical Spark Discharge Experiments.

The isolation of adenine and guanine from meteorites has been cited as evidence that these substances might have been available as “raw material” on prebiotic Earth (18). However, acid hydrolyses have been needed to release these materials, and the amounts isolated have been low (17–19). Traces of uracil have also been reported in such analyses (20), but no cytosine at all.

The formation of a substance in an electric spark discharge conducted in a simulated early atmosphere has also been regarded as a positive indication of its prebiotic availability (21). Again, low yields of adenine and guanine have been reported in such reactions, but no cytosine (22). The failure to isolate even traces of cytosine in these procedures signals the presence of some problem with its synthesis and/or stability.

Proposed Prebiotic Cytosine Syntheses.

As bonds from carbon to a hetero atom are more readily constructed than carbon–carbon bonds, cytosine syntheses have usually combined a three-carbon fragment with another bearing a urea-like carbon. The most prominent C-3 fragments used have been cyanoacetylene and its hydrolysis product, cyanoacetaldehyde. These processes are discussed separately below.

Syntheses based on cyanoacetylene.

As shown in Fig. 1(Fig.1), Ferris et al. (23) reported that 0.2 M cyanoacetylene (I) and 2 M cyanate (II) reacted together readily at 30°C to givetrans-cyanovinylurea (III) and unidentified products. Conversion of trans-cyanovinylurea to cytosine (with the cis isomer as a likely intermediate) took place readily at pH 11 or greater. In a more direct preparation, cyanate and cyanoacetylene were heated together at 100°C for 24 hr. In a typical run at low concentration, 0.025 M cyanoacetylene and 0.05 M cyanate (the stoichiometry requires two cyanates per cyanoacetylene) afforded 6% cytosine. The maximum yield observed over all circumstances was 19%.

Department of Chemistry and Biochemistry, University of California at San Diego, La Jolla, CA 92093-0506

Contributed by Stanley L. Miller

Abstract

High-temperature origin-of-life theories require that the components of the first genetic material are stable. We therefore have measured the half-lives for the decomposition of the nucleobases. They have been found to be short on the geologic time scale. At 100°C, the growth temperatures of the hyperthermophiles, the half-lives are too short to allow for the adequate accumulation of these compounds (t1/2 for A and G ≈ 1 yr; U = 12 yr; C = 19 days). Therefore, unless the origin of life took place extremely rapidly (<100 yr), we conclude that a high-temperature origin of life may be possible, but it cannot involve adenine, uracil, guanine, or cytosine. The rates of hydrolysis at 100°C also suggest that an ocean-boiling asteroid impact would reset the prebiotic clock, requiring prebiotic synthetic processes to begin again. At 0°C, A, U, G, and T appear to be sufficiently stable (t1/2 ≥ 106 yr) to be involved in a low-temperature origin of life. However, the lack of stability of cytosine at 0°C (t1/2 = 17,000 yr) raises the possibility that the GC base pair may not have been used in the first genetic material unless life arose quickly (<106 yr) after a sterilization event. A two-letter code or an alternative base pair may have been used instead.

domingo, novembro 27, 2011

James Taylor, Contributor

I write about energy and environment issues.

OP/ED

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11/23/2011 @ 11:38AM

Climategate 2.0: New E-Mails Rock The Global Warming Debate

A new batch of 5,000 emails among scientists central to the assertion that humans are causing a global warming crisis were anonymously released to the public yesterday, igniting a new firestorm of controversy nearly two years to the day after similar emails ignited the Climategate scandal.

Three themes are emerging from the newly released emails: (1) prominent scientists central to the global warming debate are taking measures to conceal rather than disseminate underlying data and discussions; (2) these scientists view global warming as a political “cause” rather than a balanced scientific inquiry and (3) many of these scientists frankly admit to each other that much of the science is weak and dependent on deliberate manipulation of facts and data.

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Regarding scientific transparency, a defining characteristic of science is the open sharing of scientific data, theories and procedures so that independent parties, and especially skeptics of a particular theory or hypothesis, can replicate and validate asserted experiments or observations. Emails between Climategate scientists, however, show a concerted effort to hide rather than disseminate underlying evidence and procedures.

“I’ve been told that IPCC is above national FOI [Freedom of Information] Acts. One way to cover yourself and all those working in AR5 would be to delete all emails at the end of the process,”writes Phil Jones, a scientist working with the United Nations Intergovernmental Panel on Climate Change (IPCC), in a newly released email.

“Any work we have done in the past is done on the back of the research grants we get – and has to be well hidden,” Jones writes in another newly released email. “I’ve discussed this with the main funder (U.S. Dept of Energy) in the past and they are happy about not releasing the original station data.”

The original Climategate emails contained similar evidence of destroying information and data that the public would naturally assume would be available according to freedom of information principles. “Mike, can you delete any emails you may have had with Keith [Briffa] re AR4 [UN Intergovernmental Panel on Climate Change 4th Assessment]?” Jones wrote to Penn State University scientist Michael Mann in an email released in Climategate 1.0. “Keith will do likewise. … We will be getting Caspar [Ammann] to do likewise. I see that CA [the Climate Audit Web site] claim they discovered the 1945 problem in the Nature paper!!”

The new emails also reveal the scientists’ attempts to politicize the debate and advance predetermined outcomes.

“The trick may be to decide on the main message and use that to guid[e] what’s included and what is left out” of IPCC reports, writes Jonathan Overpeck, coordinating lead author for the IPCC’s most recent climate assessment.

“I gave up on [Georgia Institute of Technology climate professor] Judith Curry a while ago. I don’t know what she thinks she’s doing, but its not helping the cause,” wrote Mann in another newly released email.

Ernst Mayr called the first part of the evolutionary synthesis the ‘Fisherian synthesis’ on account of the dominant role played by R.A. Fisher in forging a mathematical theory of natural selection together with J.B.S. Haldane and Sewall Wright in the decade 1922–1932. It is here argued that Fisher’s contribution relied on a close reading of Darwin’s work to a much greater extent than did the contributions of Haldane and Wright, that it was synthetic in contrast to their analytic approach and that it was greatly influenced by his friendship with the Darwin family, particularly with Charles’s son Leonard.

Structural colors are generated by scattering of light by variations in tissue nanostructure. They are widespread among animals and have been studied most extensively in butterflies and moths (Lepidoptera), which exhibit the widest diversity of photonic nanostructures, resultant colors, and visual effects of any extant organism. The evolution of structural coloration in lepidopterans, however, is poorly understood. Existing hypotheses based on phylogenetic and/or structural data are controversial and do not incorporate data from fossils. Here we report the first example of structurally colored scales in fossil lepidopterans; specimens are from the 47-million-year-old Messel oil shale (Germany). The preserved colors are generated by a multilayer reflector comprised of a stack of perforated laminae in the scale lumen; differently colored scales differ in their ultrastructure. The original colors were altered during fossilization but are reconstructed based upon preserved ultrastructural detail. The dorsal surface of the forewings was a yellow-green color that probably served as a dual-purpose defensive signal, i.e. aposematic during feeding and cryptic at rest. This visual signal was enhanced by suppression of iridescence (change in hue with viewing angle) achieved via two separate optical mechanisms: extensive perforation, and concave distortion, of the multilayer reflector. The fossils provide the first evidence, to our knowledge, for the function of structural color in fossils and demonstrate the feasibility of reconstructing color in non-metallic lepidopteran fossils.Plastic scale developmental processes and complex optical mechanisms for interspecific signaling had clearly evolved in lepidopterans by the mid-Eocene.

Author Summary

Biological structural colors are generated when light is scattered by nanostructures in tissues. Such colors have diverse functions for communication both among and between species. Structural colors are most complex in extant butterflies and moths (lepidopterans), but the evolution of such colors and their functions in this group of organisms is poorly understood. Fossils can provide insights into the evolution of biological structures, but evidence of structurally colored tissues was hitherto unknown in fossil lepidopterans. Here, we report the preservation of structurally colored scales in fossil moths with striking metallic hues from the ~47-million-year-old (Eocene) GrubeMessel oil shales (Germany). We identify the color-producing nanostructure in the scales and show that the original colors were altered during fossilization. Preserved details in the scales allow us to reconstruct the original colors and show that the dorsal surface of the forewings was yellow-green. The optical properties of the scales strongly indicate that the color functioned as a warning signal during feeding but was cryptic when the moths were at rest. Our results confirm that structural colors can be reconstructed even in non-metallic lepidopteran fossils and show that defensive structural coloration had evolved in insects by the mid-Eocene.

sábado, novembro 26, 2011

The 1909 Darwin Celebration - Reexamining Evolution in the Light of Mendel, Mutation, and Meiosis

Marsha L.
Richmond*

ABSTRACT

In June 1909, scientists and dignitaries from 167
different countries gathered in Cambridge to celebrate the hundredth anniversary of Charles
Darwin’s birth and the fiftieth anniversary of the publication of Origin of Species. The event was one
of the most magnificent commemorationsin the annals of science. Delegates gathered within the
cloisters of Cambridge University not only to honor the “hero” of evolution but
also to reassess the underpinnings of Darwinism at a critical juncture.With the mechanism
of natural selection increasingly under attack, evolutionary theory was in disarray.
Against this backdrop, biologists weighed the impact of several new developments—the
rediscovery of Mendel’s laws of heredity, de Vriesian mutation theory, and the linkage of sex-cell division
(recently named “meiosis”) to the mechanism of heredity. The 1909 Darwin
celebration thus represents a significant watershed in the history of modern biology
that allows historians to assess the status of evolution prior to the advent of the
chromosome theory of genetics.